A cortical neuropeptide with neuronal depressant and sleep-modulating properties (original) (raw)

Nature volume 381, pages 242–245 (1996)Cite this article

Abstract

ACETYLCHOLINE (ACh) plays a key role in the transitions between the different phases of sleep1: Slow-wave sleep requires low ACh concentrations in the brain, whereas rapid-eye-movement (REM) sleep is associated with high levels of ACh. Also, these phases of sleep are differentially sensitive to a number of endogenous neuropeptides and cytokines, including somatostatin, which has been shown to increase REM sleep without significantly affecting other phases2. Here we report the cloning and initial characterization of cortistatin, a neuropeptide that exhibits strong structural similarity to somatostatin, although it is the product of a different gene. Administration of cortistatin depresses neuronal electrical activity but, unlike somatostatin, induces low-frequency waves in the cerebral cortex and antagonizes the effects of acetylcholine on hippocampal and cortical measures of excitability. This suggests a mechanism for cortical synchronization related to sleep.

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References

  1. Shiromani, P. J., Gillin, J. C. & Henriksen, S. J. A. Rev. Pharmac. Toxicol. 27, 137–56 (1987).
    Article CAS Google Scholar
  2. Borbely, A. A. & Tobler, I. Physiol. Rev. 69, 605–670 (1989).
    Article CAS Google Scholar
  3. Glushankov, P. et al. Proc. natn. Acacf. Sci. U.S.A. 81, 6662–6666 (1984).
    Article ADS Google Scholar
  4. Veber, D. F. et al. Nature 280, 512–514 (1979).
    Article ADS CAS Google Scholar
  5. Erlander, M. G. et al. Neuron 7, 91–100 (1991).
    Article CAS Google Scholar
  6. Schonbrunn, A. H. & Tashijan, A. J. R., J. biol. Chem. 235, 6473–6483 (1978).
    Google Scholar
  7. Halliwell, J. V. & Adams, P. R. Brain Res. 250, 71–92 (1982).
    Article CAS Google Scholar
  8. Moore, S. D. et al. Science 239, 278–280 (1988).
    Article ADS CAS Google Scholar
  9. Schweitzer, P., Madamba, S. & Siggins, G. R. Nature 346, 464–466 (1990).
    Article ADS CAS Google Scholar
  10. Andersen, P., Bliss, T. V. P. & Skrede, K. K. Expl Brain Res. 13, 208–221 (1971).
    CAS Google Scholar
  11. Danguir, J. Brain Res. 367, 26–30 (1986).
    Article CAS Google Scholar
  12. Steriade, M., McCormick, D. A. & Sejnowski, T. J. Science 262, 679–685 (1993).
    Article ADS CAS Google Scholar
  13. Andersen, P., Eccles, J. C. & Løyning, Y. J. Neurophysiol. 27, 607–619 (1964).
    Google Scholar
  14. Kandel, E. R. & Spencer, W. A. J. Neurophysiol. 24, 243–259 (1961).
    Article CAS Google Scholar
  15. Steffensen, S. & Henriksen, S. J. Brain Res. 538, 46–53 (1991).
    Article CAS Google Scholar
  16. Maurer, R. et al. Proc. natn. Acad. Sci. U.S.A. 79, 4815–4817 (1982).
    Article ADS CAS Google Scholar
  17. Scharfman, H. E. & Schwartzkroin, P. A. Brain Res. 493, 205–211 (1989).
    Article CAS Google Scholar
  18. deLecea, L. et al. Molec. Brain Res. 25, 286–296 (1994).
    Article CAS Google Scholar
  19. Schweitzer, P. et al. J. Neurosci. 13, 2033–2049 (1993).
    Article CAS Google Scholar
  20. Prospero-Garcia, O., Criado, J. R. & Henriksen, S. J. Pharmac. Biochem. Behav. 49, 413 (1994).
    Article CAS Google Scholar
  21. Steffensen, S. C., Campbell, I. L. & Henriksen, S. J. Brain Res. 652, 149 (1994).
    Article CAS Google Scholar

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Authors and Affiliations

  1. Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, 92037, USA
    Luis de Lecea, Kaare M. Gautvik, Patria E. Danielson, Charles L. M. Dunlop & J. Gregor Sutcliffe
  2. Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California, 92037, USA
    José R. Criado, Óscar Prospero-Garcia, Paul Schweitzer, George R. Siggins & Steven J. Henriksen

Authors

  1. Luis de Lecea
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  2. José R. Criado
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  3. Óscar Prospero-Garcia
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  4. Kaare M. Gautvik
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  5. Paul Schweitzer
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  6. Patria E. Danielson
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  7. Charles L. M. Dunlop
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  8. George R. Siggins
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  9. Steven J. Henriksen
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  10. J. Gregor Sutcliffe
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de Lecea, L., Criado, J., Prospero-Garcia, Ó. et al. A cortical neuropeptide with neuronal depressant and sleep-modulating properties.Nature 381, 242–245 (1996). https://doi.org/10.1038/381242a0

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